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Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small cell lung cancer cell lines

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Journal of Integrative Medicine 2024年第4期22卷 503-514页

作者： li-hua Zhu Yu-pei liang lian Yang Feng Zhu li-jun Jia He-gen lia Department of Oncology Longhua Hospital Shanghai University of Traditional Chinese Medicine Cancer Institute of Traditional Chinese Medicine Longhua Hospital Shanghai University of Traditional Chinese Medicine Department of Laboratory Medicine Huadong Hospital Fudan University

Objective:Studies have demonstrated that cycloastragenol induces antitumor effects in prostate, colorectal and gastric cancers; however, its efficacy for inhibiting the proliferation of lung cancer cells is largely unexplored. This study explores the efficacy of cycloastragenol for inhibiting non-small cell lung cancer(NSCLC) and elucidates the underlying molecular mechanisms.Methods:The effects of cycloastragenol on lung cancer cell proliferation were assessed using an adenosine triphosphate monitoring system based on firefly luciferase and clonogenic formation assays.Cycloastragenol-induced apoptosis in lung cancer cells was evaluated using dual staining flow cytometry with an annexin V-fluorescein isothiocyanate/propidium iodide kit. To elucidate the role of cycloastragenol in the induction of apoptosis, apoptosis-related proteins were examined using Western blots.Immunofluorescence and Western blotting were used to determine whether cycloastragenol could induce autophagy in lung cancer cells. Genetic techniques, including small interfering RNA technology,were used to investigate the underlying mechanisms. The effects against lung cancer and biosafety of cycloastragenol were evaluated using a mouse subcutaneous tumor model.Results:Cycloastragenol triggered both autophagy and apoptosis. Specifically, cycloastragenol promoted apoptosis by facilitating the accumulation of phorbol-12-myristate-13-acetate-induced protein 1(NOXA), a critical apoptosis-related protein. Moreover, cycloastragenol induced a protective autophagy response through modulation of the adenosine 5?-monophosphate-activated protein kinase (AMPK)/unc-51-like autophagy-activating kinase (ULK1)/mammalian target of rapamycin (mTOR) pathway.Conclusion:Our study sheds new light on the antitumor efficacy and mechanism of action of cycloastragenol in NSCLC. This insight provides a scientific basis for exploring combination therapies that use cycloastragenol and inhibiting the AMPK/ULK1/mTOR pathway as a promising approach to combating lung cancer.

关键词： Non-small cell lung cancer Cycloastragenol Autophagy Apoptosis

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Emerging mechanisms of ferroptosis and its implications in lung cancer

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中华医学杂志(英文版) 2024年第7期137卷 818-829页

作者： li Qian Song Qibin pei Huadong Chen Yali USA State Key Laboratory of Medical Proteomics National Center for Protein Sciences (Beijing) Beijing Institute of lifeomics Beijing 102206 Cancer Center Renmin Hospital of Wuhan University Wuhan Hubei 430060 China Department of Oncology Georgetown Lombardi Comprehensive Cancer Center Georgetown University Medical Center Washington D.C. 20057

Lung cancer is one of the most common malignancies and has the highest number of deaths among all cancers. Despite continuous advances in medical strategies, the overall survival of lung cancer patients is still low, probably due to disease progression or drug resistance. Ferroptosis is an iron-dependent form of regulated cell death triggered by the lethal accumulation of lipid peroxides, and its dysregulation is implicated in cancer development. Preclinical evidence has shown that targeting the ferroptosis pathway could be a potential strategy for improving lung cancer treatment outcomes. In this review, we summarize the underlying mechanisms and regulatory networks of ferroptosis in lung cancer and highlight ferroptosis-targeting preclinical attempts to provide new insights for lung cancer treatment.

关键词： Lung cancer Ferroptosis Ferroptosis regulators Ferroptosis inducers Cancer treatment

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Disease and Economic Burden of Kashin-Beck Disease—China,2021

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China CDC weekly 2024年第2期6卷 40-44页

作者： Silu Cui Wenjun Que Zhe Jiao Qing Deng Xufeng Zhang Yanhong Cao Ning liu Ailin li Alphonse Sowanou Zhe li Tuo Wang Yang li jun Yu junrui pei NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University) Key Laboratory of Etiology and EpidemiologyEducation Bureau of Heilongjiang ProvinceInstitute of Kashin-Beck Disease ControlCenter for Endemic Disease ControlChinese Center for Disease Control and PreventionHarbin Medical UniversityHarbin CityHeilongjiang ProvinceChina NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human HealthKey Laboratory of Etiology and EpidemiologyEducation Bureau of Heilongjiang ProvinceInstitute of Endemic Fluorosis ControlCenter for Endemic Disease ControlChinese Center for Disease Control and PreventionHarbin Medical UniversityHarbin CityHeilongjiang ProvinceChina

What is already known about this topic?Kashin-Beck disease(KBD)is a chronic and degenerative osteoarthropathy characterized by cartilage degeneration.It is an endemic disease that is highly prevalent among the Chinese population and poses a significant health risk.What is added by this report?This is the first national report on the economic burden of KBD in China.According to the data from 2021,KBD has caused significant disease and economic burdens.The most substantial reduction in healthy life expectancy was observed among patients with degree II severity and those aged 60 years and older,resulting in a total indirect economic burden of 112.74 million Chinese Yuan(CNY).What are the implications for public health practice?The results of this study will contribute to informing the development of tailored prevention and control strategies by the government.These strategies will include targeted policies and recommendations for appropriate healthcare and financial subsidies,which will be based on the demographic characteristics of the endemic areas.

关键词： prevention degeneration burden

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Interpretation and characterization of rate of penetration intelligent prediction model

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Petroleum Science 2024年第1期21卷 582-596页

作者： Zhi-jun pei Xian-Zhi Song Hai-Tao Wang Yi-Qi Shi Shou-Ceng Tian Gen-Sheng li College of Petroleum Engineering China University of Petroleum(Beijing)Beijing102249China State Key Laboratory of Petroleum Resources and Prospecting Beijing102249China Kunlun Digital Technology Co. Ltd.Beijing102206China

Accurate prediction of the rate of penetration(ROP)is significant for drilling optimization.While the intelligent ROP prediction model based on fully connected neural networks(FNN)outperforms traditional ROP equations and machine learning algorithms,its lack of interpretability undermines its credibility.This study proposes a novel interpretation and characterization method for the FNN ROP prediction model using the Rectified linear Unit(ReLU)activation function.By leveraging the derivative of the ReLU function,the FNN function calculation process is transformed into vector operations.The FNN model is linearly characterized through further simplification,enabling its interpretation and analysis.The proposed method is applied in ROP prediction scenarios using drilling data from three vertical wells in the Tarim Oilfield.The results demonstrate that the FNN ROP prediction model with ReLU as the activation function performs exceptionally well.The relative activation frequency curve of hidden layer neurons aids in analyzing the overfitting of the FNN ROP model and determining drilling data similarity.In the well sections with similar drilling data,averaging the weight parameters enables linear characterization of the FNN ROP prediction model,leading to the establishment of a corresponding linear representation equation.Furthermore,the quantitative analysis of each feature's influence on ROP facilitates the proposal of drilling parameter optimization schemes for the current well section.The established linear characterization equation exhibits high precision,strong stability,and adaptability through the application and validation across multiple well sections.

关键词： Fully connected neural network Explainable artificial intelligence Rate of penetration ReLU active function Deep learning Machine learning

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Association of physical activity with risk of chronic kidney disease in China:A population-based cohort study

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Journal of Sport and Health Science 2024年第2期13卷 204-211页

作者： Kexiang Shi Yunqing Zhu jun Lv Dianjianyi Sun pei pei Huaidong Du Yiping Chen ling Yang Bing Han Rebecca Stevens junshi Chen Zhengming Chen liming li Canqing Yu China Kadoorie Biobank collaborative group Department of Epidemiology&Biostatistics School of Public HealthPeking University Health Science CenterBeijing 100191China Peking University Center for Public Health and Epidemic Preparedness&Response Beijing 100191China Key Laboratory of Epidemiology of Major Diseases(Peking University) Ministry of EducationBeijing 100191China Clinical Trial Service Unit&Epidemiological Studies Unit(CTSU) Nuffield Department of Population HealthUniversity of OxfordOxford OX37LFUK Medical Research Council Population Health Research Unit at the University of Oxford Oxford OX37LFUK NCDs Prevention and Control Department Henan Center for Disease Control and PreventionZhengzhou 450016China China National Center for Food Safety Risk Assessment Beijing 100022China 不详

Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with CKD and its subtypes in China.Methods:The study included 475,376 adults from the China Kadoorie Biobank aged 30-79 years during 2004-2008 at baseline.An interviewer-administered questionnaire was used to collect the information about PA,which was quantified as metabolic equivalent of task hours per day(MET-h/day)and categorized into 4 groups based on quartiles.Cox regression was used to analyze the association between PA and CKD risk.Results:During a median follow-up of 12.1 years,5415 incident CKD cases were documented,including 1159 incident diabetic kidney disease(DKD)cases and 362 incident hypertensive nephropathy(HTN)cases.Total PA was inversely associated with CKD risk,with an adjusted hazard ratio(HR,95%confidence interval(95%CI))of 0.83(0.75-0.92)for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile.Similar results were observed for risk of DKD and HTN,and the corresponding HRs(95%CIs)were 0.75(0.58-0.97)for DKD risk and 0.56(0.37-0.85)for HTN risk.Increased nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD,with HRs(95%CIs)of 0.80(0.73-0.88),0.85(0.77-0.94),and 0.85(0.76-0.95)in the highest quartile,respectively.Conclusion:PA,including nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA,was inversely associated with the risk of CKD,including DKD,HTN,and other CKD,and such associations were dose dependent.

关键词： Chronic kidney disease Domain Intensity Physical activity

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GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines

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World Journal of Stem Cells 2024年第5期16卷 538-550页

作者： Yang-Zhou Jiang Lan-Yue Hu Mao-Shan Chen Xiao-Jie Wang Cheng-Ning Tan pei-pei Xue Teng Yu Xiao-Yan He li-Xin Xiang Yan-Ni Xiao Xiao-liang li Qian Ran Zhong-jun li li Chen Laboratory of Radiation Biology Department of Blood TransfusionLaboratory Medicine CenterThe Second Affiliated HospitalThird Military Medical UniversityChongqing 400037China Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center Ministry of Education of the People’s Republic of ChinaChongqing 400037China

BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(Fli1)have been identified as negative regulators of ANKRD26.However,the positive regulators of ANKRD26 are still unknown.AIM To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 transcription.METHODS Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family POTE.According to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(Fli1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activity of the mitogen activated protein kinase and e

关键词： Ankyrin repeat domain containing 26 GATA binding protein 2 Thrombocytopenia 2 Transcriptional regulation Myeloid-derived cell lines

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Carbon dots-derived three-dimensional-ordered macroporous host with high penetrability and catalytic activity for LSBs under lean electrolyte

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Rare Metals 2024年第6期43卷 2560-2573页

作者： Jiao-Zi Duan Hua-Yu pei Quan Yang Xue li Xin Ba Xue Yong jun-ling Guo Si-Yu Lu Green Catalysis Center College of ChemistryZhengzhou University Country State Center for International Cooperation On Designer Low-Carbon & Environmental Materials School of Materials Science and EngineeringZhengzhou University Hubei Institute of Quality Supervision Inspection Department of Chemistry University of Sheffield

The practical energy density of lithium-sulfur batteries（LSBs） is seriously limited by the high electrolyte-to-sulfur ratios（E/S）.The E/S can be reduced by employing hosts with easy-to-infiltrate structure that ensures the uniform distribution of a lean electrolyte and high catalytic activity that can suppress "shuttle effect" via accelerating the slow conversion of soluble poly sulfides to insoluble sulfides.Among the easy-to-infiltrate structures,the three-dimensional-ordered macroporous（3DOM）structure is easier to scale preparation and more suitable for the existing industrial processes.However,it is difficult to obtain the 3DOM with（1） high penetrability due to the high viscosity of frequently-used organic polymer precursors and（2） high catalytic activity due to the low confinement effect,meaning that uniformly dispersed small-sized catalytic materials are difficult to load on 3DOM.Herein,using carbon dots（CDs） with both organic and inorganic properties as a precursor and aggregation limiting agent,a 3DOM host with high penetrability and homodispersed Ni particles of small sizes（Ni-CDs-3DOM）was synthesized.In this host:（1） CDs precursor with suitable viscosity can improve the penetrability.（2） CDs can effectively inhibit the agglomeration of Ni particles.（3） Uniformly dispersed small-size Ni particles offer high-efficiency catalytic activity toward sulfur reactions.Consequently,the Ni-CDs-3DOM/sulfur cathode exhibits high sulfur utilization and stable cycling performance even under high sulfur loading(5.5 mg·cm-1) and low E/S(6.5 μl·mg-1).This work indicates the usefulness of CDs in constructing hosts for LSBs with high energy density.

关键词： lithium–sulfur batteries Carbon dots Catalytic action Easy-to-infiltrate structure Lean electrolyte

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AWG-based large dynamic range fiber Bragg grating interrogation system

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Optoelectronics Letters 2024年第3期20卷 129-134页

作者： li Shufeng YUAN pei li Ke li Ting ZHU lianqing Key Laboratory of the Ministry of Education for Optoelectronic Measurement Technology and Instrument Beijing Information Science&Technology UniversityBeijing 100192China Beijing Laboratory of Optical Fiber Sensing and System Beijing Information Science&Technology UniversityBeijing 100016China

Arrayed waveguide gratings(AWGs) are extensively employed in fiber Bragg grating(FBG) interrogation systems due to their compact size, lightweight nature, and excellent interrogation performance. The resolution and total measurement range of AWG-based FBG interrogation systems are constrained by the output properties of AWG. We proposed an AWG-based large dynamic range interrogation system. The temperature dependence of AWG is exploited to achieve continuous interrogation. The test results show that the interrogation system has a dynamic range of 28.67 nm, an interrogation accuracy better than 25 pm, and a wavelength resolution of 6 pm.

关键词： fiber waveguide AWG

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Multi-junction cascaded vertical-cavity surface-emitting laser with a high power conversion efficiency of 74%

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light(Science & Applications) 2024年第3期13卷 555-565页

作者： Yao Xiao jun Wang Heng liu pei Miao Yudan Gou Zhicheng Zhang Guoliang Deng Shouhuan Zhou College of Electronics and Information Engineering Sichuan UniversityChengdu 610064China Suzhou Everbright Photonics Co. LtdSuzhou 215163China

High electro-optical conversion efficiency is one of the most distinctive features of semiconductor lasers as compared to other types of lasers.Its further increase remains a significant objective.Further enhancing the efficiency of edgeemitting lasers(EEL),which represent the highest efficiency among semiconductor lasers at present,is challenging.The efficiency of vertical cavity surface emitting lasers(VCSELs)has always been relatively low compared to EEL.This paper,combining modeling with experiments,demonstrates the potential of multi-junction cascaded VCSELs to achieve high efficiency beyond that of EELs,our simulations show,that a 20-junction VCSEL can achieve an efficiency of more than 88%at room temperature.We fabricated VCSEL devices with different numbers of junctions and compared their energy efficiency.15-junction VCSELs achieved a maximum efficiency of 74%at room temperature under nanosecond driving current,the corresponding differential quantum efficiency exceeds 1100%,being the largest electro-optical conversion efficiency and differential quantum efficiency reported until now for VCSELs.

关键词： cascaded power cavity

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Permanent lining castable with low bulk density and thermal conductivity:bauxite castable for tundish obtained by adding pearlescent sand

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Journal of Iron and Steel Research(International) 2024年第3期31卷 634-646页

作者： Yi Wang Jian Yang Bao Wang Hai-jun Zhang Juan Han pei-yan pei Wen-long Lv Jian-an Zhou The State Key Laboratory of Refractories and Metallurgy Wuhan University of Science and TechnologyWuhan 430081HubeiChina Key Laboratory for Ferrous Metallurgy and Resources Utilization of Ministry of Education Wuhan University of Science and TechnologyWuhan 430081HubeiChina Wuhan Research Institute of Metallurgical Construction MCCWuhan 430081HubeiChina

The low thermal conductivity and light mass of castables for tundish permanent linings are crucial for minimizing the heat loss of molten steel.In consideration of the low bulk density and thermal conductivity of pearlescent sand,the thermal insulation performance of castables was attempted to be improved by adding pearlescent sand.Pearlescent sand was modified to prevent the strength of its porous structure from deteriorating.The modification mechanism of pearlescent sand and the effect of pearlescent sand on the performance of bauxite castables were studied.The results suggested that the addition of the modified pearlescent sand significantly raised the apparent porosity and decreased the bulk density of bauxite castable.At 1000℃,the bulk density of more than 60%of the modified pearlescent sand-bauxite castable was only 2.03 g/cm^(3).The mechanical properties and thermal shock resistance of the modified pearlescent sand-bauxite castable were inferior to those of conventional bauxite castable but were adequate to meet the use conditions of casta-bles for tundish permanent linings.At high temperatures of 200-800℃,the thermal conductivity of more than 60%of the modified pearlescent sand-bauxite castable was smaller than that of conventional bauxite castable.The addition of the modified pearlescent sand can greatly reduce the thermal conductivity and bulk density of bauxite castable.

关键词： Pearlescent sand-Hydrophobic modification Bauxite castable Thermal insulation performance Mechanical property

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